This application addresses broad Challenge Area (04) Clinical Research and specific Challenge 04-DK-104 Improve the diagnosis, staging and treatment of diseases of the liver. This application specifically seeks to develop an approach that will improve the diagnosis of acute liver failure in infants, result in significantly improved outcome with medical therapy, and reduce the utilization of liver transplantation in pediatric patients. Neonatal hemochromatosis (NH) is the leading diagnosed cause of liver failure in neonates in most series. However, no diagnosis for acute liver failure can be established in up to 40% of infants. The overall objective of this application is to determine the true prevalence of NH as a cause of acute liver failure in infants d 90 days of age. The critical gap in scientific knowledge to be overcome before its importance as cause of acute liver failure can be determined is the lack of a sensitive and specific diagnostic biomarker for NH. Since NH is caused by maternal alloimmunity against fetal liver, the biomarker proposed is the presence of "anti-fetal hepatocyte IgG antibody" in mothers'or infants'serum. The diagnostic utility of an immunofluorescence assay for this biomarker is to be established and then it will be used to assess the prevalence of NH in a population of young infants with acute liver failure. Normally acquiring a study population large enough to power such a study would require many years of study. However, sera obtained from the Pediatric Acute Liver Failure study repository will be used, making it feasible to complete the proposed work within the timeframe of two years. The expected results will show that NH constitutes fully 50% of all causes of acute liver failure in young infants. This finding will have a significant positive impact because NH is responsive to specific medical therapy, which improves outcome over current treatment including liver transplantation. Furthermore, should the novel test used in this analysis prove to be sensitive and specific for the diagnosis, it could replace current diagnostic approaches and prospectively improve diagnostic accuracy in this setting. Thus, early, precise diagnosis could lead to improved outcome and reduced utilization of liver transplantation. PUBLIC HEALTH RELEVANCE: Neonatal Hemochromatosis (NH) is an important cause of liver failure in infants, but the diagnosis may be easily missed. A novel serological test will be used to determine if NH is the cause of the nearly 40% of pediatric acute liver failure without diagnosis. Since NH is responsive to medical treatment, improving the diagnosis of acute liver failure could save the lives of many infants and substantially reduce the need for liver transplantation in children.